Pathophysiology

Genetics, the environment, and drugs...oh my!

As was previously discussed last week, there are several factors that when converged in the perfect storm can result in a diagnosis of schizophrenia. Genetics plays a crucial role, and even though it is not fully understood which genes are responsible for schizophrenia, we know having a direct relative with schizophrenia is the biggest risk factor for someone becoming diagnosed with the disease. We know the environment of the pregnant mother can play a role on the fetus developing schizophrenia later on, and we also know drugs, such as amphetamines, cocaine, and marijuana, can also induce psychosis.1 But what is happening in the brain that causes this psychosis? What makes the brain of a person with schizophrenia different from the brain of someone without the disease? As with the genes responsible for schizophrenia, there is a lot of research currently going on to answer these questions.

What research has found is that people with schizophrenia tend to have problems with certain neurotransmitters. This research has led to the dysregulation hypothesis, which says that the psychotic symptoms involved with schizophrenia are the result of impairment or malfunction of neurotransmitters.2 One of these neurotransmitters is dopamine. Dopamine is a neurohormone, or neurotransmitter, that is often referred to in layman's terms as a "feel good" hormone. When there is too much dopamine in the brain, a person will often suffer from psychotic symptoms such as hallucinations or delusions. This is why certain illicit drugs induce psychosis, because they increase the amount of dopamine in the brain in the extracellular space. Another neurotransmitter that when malfunctioning can lead to schizophrenia is glutamate and its reciprocal NMDA receptor.3 It is hypothesized that the impaired binding of glutamate to the NMDA receptor can then lead to the increased levels of dopamine later on.4 This is better explained by Dr. Shitij Kapur from King's College in London: 

References:

1: NAMI - The National Alliance on Mental Illness. (n.d.). Retrieved January 23, 2015, from http://www.nami.org/Content/NavigationMenu/Mental_Illnesses/Schizophrenia9/Causes.htm

2: Stuart, G. (2013). Chapter 20: Neurobiological Responses and Schizophrenia and Psychotic Disorders. In Principles and practice of psychiatric nursing (10th ed., pp. 344-375). Maryland Heights, Mo.: Elsevier Saunders.

3: de Bartolomeis, A., Iasevoli, F., Tomasetti, C., & Buonaguro, E. F. (2014). Micrornas in schizophrenia: Implications for synaptic plasticity and dopamine–glutamate interaction at the postsynaptic density. New avenues for antipsychotic treatment under a theranostic perspective. Molecular Neurobiology, doi:10.1007/s12035-014-8962-8

4/Movie: Roche. (2013, October 2). The Biology Behind Schizophrenia [Video file]. Retrieved from https://www.youtube.com/watch?v=V1kSIfxBVfU